JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate Academic Article uri icon

Overview

MeSH Major

  • Adenocarcinoma
  • Cell Transformation, Neoplastic
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Signaling System
  • PTEN Phosphohydrolase
  • Prostatic Neoplasms

abstract

  • The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (Pten) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (ΔJnk ΔPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (ΔPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (ΔMkk4 ΔMkk7 ΔPten mice) causes rapid development of invasive adenocarcinoma. We found that JNK signaling defects cause an androgen-independent expansion of the immature progenitor cell population in the primary tumor. The JNK-deficient progenitor cells display increased proliferation and tumorigenic potential compared with progenitor cells from control prostate tumors. These data demonstrate that the JNK and PTEN signaling pathways can cooperate to regulate the progression of prostate neoplasia to invasive adenocarcinoma.

publication date

  • July 24, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3409732

Digital Object Identifier (DOI)

  • 10.1073/pnas.1209660109

PubMed ID

  • 22753496

Additional Document Info

start page

  • 12046

end page

  • 51

volume

  • 109

number

  • 30